【作者】 李东杰；

【导师】 张东峰； 刘成玉；

【作者基本信息】 青岛大学 ， 临床检验诊断学， 2009， 硕士

【摘要】 目的探讨eNOS基因G894T变异和AGT基因M235T变异与超重及腰臀比异常之间的交互作用对原发性高血压的影响。方法以青岛市区四个社区人群健康查体中筛检出的、未经药物系统治疗的235名原发性高血压患者及240名正常血压者为调查对象;用聚合酶链反应—限制性片段长度多态性(PCR—RFLP)方法检测eNOS基因G894T多态性及AGT基因M235T多态性;用相加模型分别分析基因多态性变异与超重及腰臀比异常之间的交互作用。结果高血压组eNOS基因T等位基因频率(18.94%)及AGT基因T等位基因频率(46.81%)高于对照组(12.71%,37.71%),(χ~2=6.927,8.677,P＜0.01);高血压组超重率(86.81%)及腰臀比异常率(69.79%)高于对照组(70.83%,47.92%),(χ~2=18.100,23.433,P＜0.001)。用多因素Logistic回归调整年龄、性别、体质指数、吸烟及饮酒、血脂等混杂因素后,eNOS基因G894T基因变异与腰臀比异常间存在正交互作用,其协同效应指数(S)为1.542,归因交互效应[I(AB)]为0.909,归因交互效应百分比(AP%)为25.34%,纯因子间归因交互效应百分比(AP~*%)为35.14%;AGT基因T等位基因与腰臀比异常亦有正交互作用,调整上述混杂因素后其以上指数分别为1.930、1.560、36.82%、48.19%;AGT基因T等位基因与超重亦有正交互作用,调整混杂后其以上指数分别为2.241、0.598、28.75%、55.37%。此外,eNOS基因T等位基因与AGT基因T等位基因亦有正交互作用,调整混杂后其以上指数分别为1.600、1.520、30.07%、37.48%。结论eNOS基因T等位基因、AGT基因T等位基因、超重与腰臀比异常是原发性高血压发生的危险因素;eNOS基因T等位基因、AGT基因T等位基因与腰臀比异常之间的交互作用在该研究人群高血压患病中具有重要意义。在携带eNOS基因T等位基因或AGT基因T等位基因同时伴有腰臀比异常的人群中,控制腰臀比异常可明显降低居民原发性高血压患病的危险性。更多还原

【Abstract】 Objective To analyze the effects of G894T(Glu298Asp) mutation in eNOS gene, M235T mutation in AGT gene and abnormality of waist-to-hip ratio(WHR),overweight and the interactions between the four factors on essential hypertension(EH).Methods The study population came from a screening survey carried out in four communities in Qingdao.A total of 235 patients diagnosed as essential hypertension, without anti-hypertensive medication,and 240 healthy subjects were enrolled in the current study.Polymerase chain reaction(PCR) and restriction fragment length polymorphism(RFLP) were performed to detect the polymorphism of G894T in the endothelial nitric oxide synthase(eNOS ) gene and M235T in the angiotensinogen(AGT) gene.Additive model was used to analyze the interactions between these genes and overweight or abnormal Waist-to-Hip Ratio(WHR).Results eNOS gene T allele frequency(18.94%) and AGT gene T allele frequency (46.81%) in patients were significantly higher than those in controls(12.71%, 37.71%),(χ~2=6.927,8.677,P＜0.01 );The frequency of overweight(86.81%) and frequency of abnormality of WHR(69.79%) in patients were significantly higher than those in controls(70.83%,47.92%),(χ~2=18.100,23.433,P＜0.001).After adjusting age,gender,drinking,smoking,body mass index and blood fats by logistic regression,G894T mutation of eNOS gene and abnormality of WHR showed a positive interaction.Synergy index between the G894T mutation in eNOS gene and Abnormality of WHR was 1.542,attributable interaction was 0.909,attributable interaction percentage was 25.34%,pure attributable interaction percentage was 35.14 %.M235T mutation of AGT gene and abnormality of WHR also showed a positive interaction.After adjusting the confounding factors mentioned above by logistic regression,the indexes mentioned above were 1.930,1.560,36.82%and 48.19% respectively.There was also a positive interaction between M235T mutation in AGT gene and overweight,the indexes were 2.241,0.598,28.75%and 55.37%respectively after adjustment of confounding factors by logistic regression.In addition,there was also a positive interaction between polymorphisms of T allele of eNOS and T allele of AGT,the indexes were 1.600,1.520,30.07%and 37.48%respectivelyafter adjustment of confounding factors by logistic regression. Conclusions T allele of eNOS,T allele of AGT,overweight and abnormality of WHR were the risk factors of essential hypertension.The interactions among T allele of eNOS,T allele of AGT and abnormality of WHR had positive effects on essential hypertension in this studied population.To control abnormality of WHR in the population who had T allele of eNOS or T allele of AGT and abnormality of WHR simultaneously could produce marked decrease of getting essential hypertension in general population.更多还原